harr hema leukocytes

1. Which of the following is an unusual complication

that may occur in infectious mononucleosis?

A. Splenic infarctions

B. Dactylitis

C. Hemolytic anemia

D. Giant platelets

1. C Occasionally patients with infectious mononucleosis

develop a potent cold agglutinin with anti-I specificity.

This cold autoantibody can cause strong hemolysis

and a hemolytic anemia.

2. In a patient with human immunodeficiency virus

(HIV) infection, one should expect to see:

A. Shift to the left in WBCs

B. Target cells

C. Reactive lymphocytes

D. Pelgeroid cells

2. C HIV infection brings about several hematological

abnormalities seen on peripheral smear examination;

most patients demonstrate reactive lymphocytes and

have granulocytopenia.

3. Which inclusions may be seen in leukocytes?

A. Döhle bodies

B. Basophilic stippling

C. Malarial parasites

D. Howell-Jolly bodies

3. A Döhle bodies are RNA-rich areas within

polymorphonuclear neutrophils (PMNs) that are

oval and light blue in color. Although often

associated with infectious states, they are seen in

a wide range of conditions and toxic reactions,

including hemolytic and pernicious anemias,

chronic granulocytic leukemia, and therapy with

antineoplastic drugs. The other inclusions are

associated with erythrocytes.

4. Which of the following is contained in the primary

granules of the neutrophil?

A. Lactoferrin

B. Myeloperoxidase

C. Histamine

D. Alkaline phosphatase

4. B Myeloperoxidase, lysozyme, and acid phosphatase

are enzymes that are contained in the primary

granules of neutrophils. The contents of secondary

and tertiary granules include lactoferrin, collagenase,

NADPH oxidase, and alkaline phosphatase

5. What is the typical range of relative lymphocyte

percentage in the peripheral blood smear of a

1-year-old child?

A. 1%-6%

B. 27%-33%

C. 35%-58%

D. 50%-70%

5. D The mean relative lymphocyte percentage for a

1-year-old child is 61% compared to the mean

lymphocyte percentage of 35% for an adult.

6. Qualitative and quantitative neutrophil changes

noted in response to infection include all of the

following except:

A. Neutrophilia

B. Pelgeroid hyposegmentation

C. Toxic granulation

D. Vacuolization

6. B Neutrophil changes associated with infection may

include neutrophilia, shift to the left, toxic

granulation, Döhle bodies, and vacuolization.

Pelgeroid hyposegmentation is noted in neutrophils

from individuals with the congenital Pelger-Huët

anomaly and as an acquired anomaly induced by

drug ingestion or secondary to conditions such as

leukemia.

7. Neutropenia is present in patients with which

absolute neutrophil counts?

A. <1.5 × 109/L

B. <5.0 × 109/L

C. <10.0 × 109/L

D. <15.0 × 109/L

7. A Neutropenia is defined as an absolute decrease in the

number of circulating neutrophils. This condition is

present in patients having neutrophil counts of less

than 1.5 × 109/L.

8. The morphological characteristic(s) associated

with the Chédiak-Higashi syndrome is (are):

A. Pale blue cytoplasmic inclusions

B. Giant lysosomal granules

C. Small, dark-staining granules and condensed

nuclei

D. Nuclear hyposegmentation

8. B Chédiak-Higashi syndrome is a disorder of

neutrophil phagocytic dysfunction caused by

depressed chemotaxis and delayed degranulation.

The degranulation disturbance is attributed to

interference from the giant lysosomal granules

characteristic of this disorder.

9. The familial condition of Pelger-Huët anomaly is

important to recognize because this disorder must

be differentiated from:

A. Infectious mononucleosis

B. May-Hegglin anomaly

C. A shift-to-the-left increase in immature

granulocytes

D. G6PD deficiency

9. C Pelger-Huët anomaly is a benign familial condition

reported in 1 out of 6,000 individuals. Care must be

taken to differentiate Pelger-Huët cells from the

numerous band neutrophils and metamyelocytes

that may be observed during severe infection or a

shift-to-the-left of immaturity in granulocyte stages.

10. SITUATION: A differential shows reactive

lymphocytes, and the physician suspects a viral

infection is the cause. What is the expected

laboratory finding in a patient with a

cytomegalovirus (CMV) infection?

A. Heterophile antibody: positive

B. Epstein-Barr virus (EBV)-immunoglobulin

(IgM): positive

C. Direct antiglobulin test (DAT): positive

D. CMV-IgM: positive

10. D If both the heterophile antibody test and the

EBV-IgM tests are negative in a patient with reactive

lymphocytosis and a suspected viral infection, the

serum should be analyzed for IgM antibodies to

CMV. CMV belongs to the herpes virus family and is

endemic worldwide. CMV infection is the most

common cause of heterophile-negative infectious

mononucleosis.

11. Neutrophil phagocytosis and particle ingestion are

associated with an increase in oxygen utilization

called respiratory burst. What are the two most

important products of this biochemical reaction?

A. Hydrogen peroxide and superoxide anion

B. Lactoferrin and NADPH oxidase

C. Cytochrome b and collagenase

D. Alkaline phosphatase and ascorbic acid

11. A The biochemical products of the respiratory burst

that are involved with neutrophil particle ingestion

during phagocytosis are hydrogen peroxide and

superoxide anion. The activated neutrophil

discharges the enzyme NADPH oxidase into the

phagolysosome, where it converts O2 to superoxide

anion (O2

-), which is then reduced to hydrogen

peroxide (H2O2).

12. Which of the morphological findings are

characteristic of reactive lymphocytes?

A. High nuclear:cytoplasmic ratio

B. Prominent nucleoli

C. Basophilic cytoplasm

D. All of these options

12. D Both reactive lymphocytes and blasts may have

basophilic cytoplasm, a high N:C ratio, and the

presence of prominent nucleoli. Blasts, however,

have an extremely fine nuclear chromatin staining

pattern as viewed on a Wright's-Giemsa's—stained

smear.

1. Auer rods may be seen in all of the following

except:

A. Acute myelomonocytic leukemia (M4)

B. Acute lymphoblastic leukemia

C. Acute myeloid leukemia without maturation (M1)

D. Acute promyelocytic leukemia (M3)

1. B Auer rods are not seen characteristically in

lymphoblasts. They may be seen in myeloblasts,

promyelocytes, and monoblasts.

2. Which type of anemia is usually present in a

patient with acute leukemia?

A. Microcytic, hyperchromic

B. Microcytic, hypochromic

C. Normocytic, normochromic

D. Macrocytic, normochromic

2. C Acute leukemia is usually associated with a

normocytic normochromic anemia. Anemia in

acute leukemia is usually present from the onset

and may be severe; however, there is no inherent

nutritional deficiency leading to either a microcytic,

hypochromic, or megaloblastic process.

3. In leukemia, which term describes a peripheral

blood finding of leukocytosis with a shift to the

left, accompanied by nucleated red cells?

A. Myelophthisis

B. Dysplasia

C. Leukoerythroblastosis

D. Megaloblastosis

3. C The presence of immature leukocytes and nucleated

red cells is called leukoerythroblastosis and frequently

denotes a malignant or myeloproliferative process.

Myelophthisis refers to replacement of bone marrow

by a disease process such as a neoplasm. The

development of abnormal tissue is called dysplasia.

4. The basic pathophysiological mechanisms

responsible for producing signs and symptoms in

leukemia include all of the following except:

A. Replacement of normal marrow precursors by

leukemic cells causing anemia

B. Decrease in functional leukocytes causing

infection

C. Hemorrhage secondary to thrombocytopenia

D. Decreased erythropoietin production

4. D A normal physiological response to anemia would

be an increase in the kidney's production of

erythropoietin. The accumulation of leukemic cells

in the bone marrow leads to marrow failure, which

is manifested by anemia, thrombocytopenia, and

granulocytopenia.

5. Which type of acute myeloid leukemia is called

the true monocytic leukemia and follows an acute

or subacute course characterized by monoblasts,

promonocytes, and monocytes?

A. Acute myeloid leukemia, minimally differentiated

B. Acute myeloid leukemia without maturation

C. Acute myelomonocytic leukemia

D. Acute monocytic leukemia

5. D Acute monocytic leukemia has an incidence of

between 1%-8% of all acute leukemias. It has a

distinctive clinical manifestation of monocytic

involvement resulting in skin and gum hyperplasia.

The WBC count is markedly elevated, and prognosis

is poor.

6. In which age group does acute lymphoblastic

leukemia occur with the highest frequency?

A. 1-15 years

B. 20-35 years

C. 45-60 years

D. 60-75 years

6. A Acute lymphoblastic leukemia (ALL) usually affects

children from ages 1-15 and is the most common

type of acute leukemia in this age group. In addition,

ALL constitutes the single most prevalent malignancy

in pediatric patients.

7. Disseminated intravascular coagulation (DIC) is

most often associated with which of the following

types of acute leukemia?

A. Acute myeloid leukemia without maturation

B. Acute promyelocytic leukemia

C. Acute myelomonocytic leukemia

D. Acute monocytic leukemia

7. B The azurophilic granules in the leukemic promyelocytes

in patients with acute promyelocytic leukemia contain

thromboplastic substances. These activate soluble

coagulation factors, which when released into the

blood, cause DIC.

8. An M:E ratio of 10:1 is most often seen in:

A. Thalassemia

B. Leukemia

C. Polycythemia vera

D. Myelofibrosis

8. B A disproportionate increase in the myeloid

component of the bone marrow is usually the

result of a leukemic state. The normal M:E ratio is

approximately 4:1 in adults with normal cellularity.

9. Which of the following is a characteristic of

Auer rods?

A. They are composed of azurophilic granules

B. They stain periodic acid-Schiff (PAS) positive

C. They are predominantly seen in chronic

myelogenous leukemia (CML)

D. They are nonspecific esterase positive

9. A Auer rods are a linear projection of primary

azurophilic granules, and are present in the

cytoplasm of myeloblasts and monoblasts in

patients with acute leukemia.

10. SITUATION: The following laboratory values

are seen:

WBCs = 6.0 × 109/L Hgb = 6.0 g/dL

RBCs = 1.90 × 1012/L Hct = 18.5%

Platelets = 130 × 109/L

Serum vitamin B12 and folic acid: normal

WBC Differential Bone Marrow

6% PMNs 40% myeloblasts

40% lymphocytes 60% promegaloblasts

4% monocytes 40 megaloblastoid

NRBCs/100 WBCs

50% blasts

These results are most characteristic of:

A. Pernicious anemia

B. Acute myeloid leukemia without maturation

C. Acute erythroid leukemia

D. Acute myelomonocytic leukemia

10. C In acute erythroid leukemia, more than 50% of

nucleated bone marrow cells are erythroid and more

than 30% nonerythroid cells are blasts. Pernicious

anemia results in pancytopenia and low vitamin B12

concentrations.

11. A 24-year-old man with Down syndrome presents

with a fever, pallor, lymphadenopathy, and

hepatosplenomegaly. His CBC results are as

follows:

WBCs = 10.8 × 109/L RBCs = 1.56 × 1012/L

8% PMNs Hgb = 3.3 g/dL

25% lymphocytes Hct = 11%

67% PAS-positive blasts Platelets = 2.5 × 109/L

These findings are suggestive of:

A. Hodgkin's lymphoma

B. Myeloproliferative disorder

C. Leukemoid reaction

D. Acute lymphocytic leukemia

11. D Common signs of acute lymphocytic leukemia are

hepatosplenomegaly (65%), lymphadenopathy (50%),

and fever (60%). Anemia and thrombocytopenia are

usually present and the WBC count is variable. The

numerous lymphoblasts are generally PAS positive.

12. SITUATION: A peripheral smear shows 75%

blasts. These stain positive for both Sudan Black B

(SBB) and peroxidase. Given these values, which

of the following disorders is most likely?

A. Acute myelocytic leukemia (AML)

B. CML

C. Acute undifferentiated leukemia (AUL)

D. Acute lymphocytic leukemia (ALL

12. A AML blasts stain positive for Sudan Black B and

peroxidase. Usually, fewer than 10% blasts are

found in the peripheral smear of patients with CML,

unless there has been a transition to blast crisis. The

organelles in the cells of AUL are not mature enough

to stain positive for SBB or peroxidase. Blasts in ALL

are characteristically negative with these stains.

13. In myeloid cells, the stain that selectively identifies

phospholipid in the membranes of both primary

and secondary granules is:

A. PAS

B. Myeloperoxidase

C. Sudan Black B stain

D. Terminal deoxynucleotidyl transferase (TdT)

13. C Phospholipids, neutral fats, and sterols are stained by

Sudan Black B. The PAS reaction stains intracellular

glycogen. Myeloperoxidase is an enzyme present in

the primary granules of myeloid cells and to a lesser

degree in monocytic cells. Terminal deoxynucleotidyl

transferase is a DNA polymerase found in thymusderived

and some bone marrow-derived

lymphocytes.

14. Sodium fluoride may be added to the naphthyl

ASD acetate (NASDA) esterase reaction. The

fluoride is added to inhibit a positive reaction

with:

A. Megakaryocytes

B. Monocytes

C. Erythrocytes

D. Granulocytes

14. B NASDA stains monocytes (and monoblasts) and

granulocytes (and myeloblasts). The addition of

fluoride renders the monocytic cells (and blasts)

negative, thus allowing for differentiation from the

granulocytic cells, which remain positive.

15. Leukemic lymphoblasts reacting with anti-CALLA

are characteristically seen in:

A. B-cell ALL

B. T-cell ALL

C. Null-cell ALL

D. Common ALL

15. D The majority of non-T, non-B ALL blast cells display

the common ALL antigen (CALLA) marker.

Lymphoblasts of common ALL are TdT positive and

CALLA positive but do not have surface membrane

IgM or μ chains and are pre-B lymphoblasts.

Common ALL has a lower relapse rate and better

prognosis than other immunologic subtypes of

B-cell ALL.

16. Which of the following reactions are often positive

in ALL but are negative in AML?

A. Terminal deoxynucleotidyl transferase and PAS

B. Chloroacetate esterase and nonspecific esterase

C. Sudan Black B and peroxidase

D. New methylene blue and acid phosphatase

16. A PAS is positive in about 50% of ALL with L1 and

L2 morphology but is negative in ALL with L3

morphology (B-cell ALL). Terminal deoxynucleotidyl

transferase is positive in all types of ALL except L3.

Both terminal deoxynucleotidyl transferase and PAS

are negative in AML.

17. A patient's peripheral blood smear and bone

marrow both show 70% blasts. These cells are

negative for Sudan Black B stain. Given these data,

which of the following is the most likely diagnosis?

A. Acute myeloid leukemia

B. Chronic lymphocytic leukemia

C. Acute promyelocytic leukemia

D. Acute lymphocytic leukemia

17. D Sudan Black B stains phospholipids and other neutral

fats. It is the most sensitive stain for granulocytic

precursors. Lymphoid cells rarely stain positive for it.

Because 70% lymphoblasts would never be seen in

CLL, the correct response is ALL.

18. Which of the following leukemias are included in

the 2008 World Health Organization classification

of myeloproliferative neoplasms?

A. Chronic myelogenous leukemia (CML)

B. Chronic neutrophilic leukemia (CNL)

C. Chronic eosinophilic leukemia (CEL)

D. All of these options are classified as

myeloproliferative neoplasms (MPN)

18. D The 2008 WHO classification system includes the

following disorders under the myeloproliferative

neoplasms (MPN): chronic myelogenous leukemia

(CML), chronic neutrophilic leukemia (CNL),

chronic eosinophilic leukemia (CEL), essential

thrombocythemia (ET), polycythemia vera

(PV), primary (idiopathetic) myelofibrosis,

hypereosinophilic syndrome, mast cell disease,

and MPNs unclassified.

19. In addition to morphology, cytochemistry, and

immunophenotyping, the WHO classification of

myelo- and lymphoproliferative disorders is based

upon which characteristic?

A. Proteomics

B. Cytogenetic abnormalities

C. Carbohydrate-associated tumor antigen

production

D. Cell signaling and adhesion markers

19. B In addition to morphology, cytochemical stains, and

flow cytometry, the WHO classification relies heavily

on chromosomal and molecular abnormalities

20. The WHO classification requires what percentage

for the blast count in the blood or bone marrow

for the diagnosis of AML?

A. At least 30%

B. At least 20%

C. At least 10%

20. B The WHO classification of AML requires that ≥20% of

nucleated bone marrow cells be blasts, while the

FAB classification generally requires ≥30%. WHO

classifies AML into five subgroups: These are acute

myeloid leukemias with recurrent genetic disorders;

acute myeloid leukemia with multilineage dysplasia;

acute myeloid leukemia and myelodysplastic

syndromes, therapy related; acute myeloid leukemia

not otherwise categorized; and acute leukemia of

ambiguous lineage

21. What would be the most likely designation

by the WHO for the FAB AML M2 by the

French-American-British classification?

A. AML with t(15;17)

B. AML with mixed lineage

C. AML with t(8;21)

D. AML with inv(16)

21. C AML with t(8;21) is classified under the category of

AML with Recurrent Genetic Abnormalities by the

WHO. This translocation occurs in up to 15% of

cases of AML and may be the most common

translocation. The AML1-ETO translocation occurs

chiefly in younger patients and often in cases of

acute myeloblastic leukemia with maturation,

FAB M2. The translocation involves the fusion of

the AML1 gene on chromosome 21 with the ETO

gene on chromosome 8.

22. What would be the most likely designation

by the WHO for the FAB AML M3 by the

French-American-British classification?

A. AML with t(15;17)

B. AML with mixed lineage

C. AML with t(8;21)

D. AML with inv(16)

22. A AML with t(15;17) is classified under the category of

AML with Recurrent Genetic Abnormalities by the

WHO. Acute promyelocytic leukemia (PML; known as

M3 under the FAB system) is composed of abnormal

promyelocytes with heavy granulation, sometimes

obscuring the nucleus, and abundant cytoplasm.

Acute promyelocytic leukemia (APL) contains a

translocation that results in the fusion of a

transcription factor called PML on chromosome

15 with the alpha (α)-retinoic acid receptor gene

(RARα) on chromosome 17.

23. Which AML cytogenetic abnormality is associated

with acute myelomonocytic leukemia with marrow

eosinophilia under the WHO classification of

AML with recurrent genetic abnormalities?

A. AML with t(15;17)

B. AML with mixed lineage

C. AML with t(8;21)

D. AML with inv(16)

23. D AML with inv(16) has pericentric inversion of

chromosome 16, and is associated with acute

myelomonocytic leukemia with marrow eosinophilia,

M4eo under the FAB system. The inv(16) results in the

fusion of the CBFβ gene on 16q22 with the MYH11

gene on 16p13.

24. What would be the most likely classification

by the WHO for the FAB AML M7 by the

French-American-British classification?

A. Acute myeloid leukemias with recurrent genetic

abnormalities

B. Acute myeloid leukemia with multilineage

dysplasia

C. Acute myeloid leukemia not otherwise

categorized

D. Acute leukemias of ambiguous lineage

24. C Acute megakaryoblastic leukemia, which is

equivalent to FAB M7, is a relatively uncommon form

of leukemia characterized by neoplastic proliferation

of megakaryoblasts and atypical megakaryocytes.

Recognition of this entity was aided by the use of

platelet peroxidase (PPO) ultrastructural studies. PPO,

which is distinct from myeloperoxidase, is specific for

the megakaryocytic cell line. Acute megakaryoblastic

leukemia is defined as an acute leukemia in which

greater than or equal to 50% of the blasts are of

megakaryocytic lineage.

1. Repeated phlebotomy in patients with

polycythemia vera (PV) may lead to the

development of:

A. Folic acid deficiency

B. Sideroblastic anemia

C. Iron deficiency anemia

D. Hemolytic anemia

1. C The most common treatment modality utilized in

PV is phlebotomy. Reduction of blood volume

(usually 1 unit of whole blood—450 cc), can be

performed weekly or even twice weekly in younger

patients to control symptoms. The Hct target range

is less than 45% for men, less than 42% for women.

Iron deficiency anemia is a predictable complication

of therapeutic phlebotomy because approximately

250 mg of iron is removed with each unit of blood.

2. In essential thrombocythemia, the platelets are:

A. Increased in number and functionally abnormal

B. Normal in number and functionally abnormal

C. Decreased in number and functional

D. Decreased in number and functionally abnormal

2. A In essential thrombocythemia, the platelet count is

extremely elevated. These platelets are abnormal in

function, leading to both bleeding and thrombotic

diathesis.

3. Which of the following cells is considered

pathognomonic for Hodgkin's disease?

A. Niemann-Pick cells

B. Reactive lymphocytes

C. Flame cells

D. Reed-Sternberg cells

3. D The morphological common denominator in

Hodgkin's lymphoma is the Reed-Sternberg (RS) cell.

It is a large, binucleated cell with a dense nucleolus

surrounded by clear space. These characteristics give

the RS cell an "owl's eye" appearance. Niemann-Pick

cells (foam cells) are histiocytes containing

phagocytized sphingolipids that stain pale blue and

impart a foamlike texture to the cytoplasm. Flame

cells are plasma cells with distinctive red cytoplasm.

They are sometimes seen in the bone marrow of

patients with multiple myeloma.

4. In myelofibrosis, the characteristic abnormal red

blood cell morphology is that of:

A. Target cells

B. Schistocytes

C. Teardrop cells

D. Ovalocytes

4. C The marked amount of fibrosis, both medullary and

extramedullary, accounts for the irreversible red cell

morphological change to a teardrop shape. The red

cells are "teared" as they attempt to pass through the

fibrotic tissue.

5. PV is characterized by:

A. Increased plasma volume

B. Pancytopenia

C. Decreased oxygen saturation

D. Absolute increase in total red cell mass

5. D The diagnosis of PV requires the demonstration of an

increase in red cell mass. Pancytosis may also be seen

in about two thirds of PV cases. The plasma volume is

normal or slightly reduced, and the arterial oxygen

saturation is usually normal.

6. Features of secondary polycythemia include all of

the following except:

A. Splenomegaly

B. Decreased oxygen saturation

C. Increased red cell mass

D. Increased erythropoietin

6. A Splenomegaly is a feature of PV but not characteristic

of secondary polycythemia. The red cell mass is

increased in both primary polycythemia (PV) and

secondary polycythemia. Erythropoietin is increased

and oxygen saturation is decreased in secondary

polycythemia.

7. The erythrocytosis seen in relative polycythemia

occurs because of:

A. Decreased arterial oxygen saturation

B. Decreased plasma volume of circulating blood

C. Increased erythropoietin levels

D. Increased erythropoiesis in the bone marrow

7. B Relative polycythemia is caused by a reduction of

plasma rather than an increase in red blood cell

volume or mass. Red cell mass is increased in both

PV and secondary polycythemia, but erythropoietin

levels are high only in secondary polycythemia

8. In PV, what is characteristically seen in the

peripheral blood?

A. Panmyelosis

B. Pancytosis

C. Pancytopenia

D. Panhyperplasia

8. B PV is a myeloproliferative disorder characterized by

uncontrolled proliferation of erythroid precursors.

However, production of all cell lines is usually

increased. Panhyperplasia is a term used to describe

the cellularity of the bone marrow in PV.

9. The leukocyte alkaline phosphatase (LAP) stain on

a patient gives the following results

10(0) 48(1+) 38(2+) 3(3+) 1(4+)

Calculate the LAP score.

A. 100

B. 117

C. 137

D. 252

9. C One hundred mature neutrophils are counted and

scored. The LAP score is calculated as: (the number

of 1+ cells × 1) + (2+ cells × 2) + (3+ cells × 3) +

(4+ cells × 4). That is, 48 + 76 + 9 + 4 = 137. The

reference range is approximately 20-130.

10. CML is distinguished from leukemoid reaction by

which of the following?

A. CML: low LAP; leukemoid: high LAP

B. CML: high LAP; leukemoid: low LAP

C. CML: high WBC; leukemoid: normal WBC

D. CML: high WBC; leukemoid: higher WBC

10. A CML causes a low LAP score, whereas an elevated

or normal score occurs in a leukemoid reaction. CML

cannot be distinguished by WBC count because both

CML and leukemoid reaction have a high count.

11. Which of the following occurs in idiopathic

myelofibrosis (IMF)?

A. Myeloid metaplasia

B. Leukoerythroblastosis

C. Fibrosis of the bone marrow

D. All of these options

11. D Anemia, fibrosis, myeloid metaplasia, thrombocytosis,

and leukoerythroblastosis occur in idiopathic

myelofibrosis.

12. What influence does the Philadelphia (Ph1)

chromosome have on the prognosis of patients

with chronic myelocytic leukemia?

A. It is not predictive

B. The prognosis is better if Ph1 is present

C. The prognosis is worse if Ph1 is present

D. The disease usually transforms into AML when

Ph1 is present

12. B Ninety percent of patients with CML have the

Philadelphia chromosome. This appears as a long

arm deletion of chromosome 22, but is actually

a translocation between the long arms of

chromosomes 22 and 9. The ABL oncogene from

chromosome 9 forms a hybrid gene with the bcr

region of chromosome 22. This results in production

of a chimeric protein with tyrosine kinase activity

that activates the cell cycle. The prognosis for CML

is better if the Philadelphia chromosome is present.

Often, a second chromosomal abnormality occurs

in CML before blast crisis.

13. Which of the following is (are) commonly found

in CML?

A. Many teardrop-shaped cells

B. Intense LAP staining

C. A decrease in granulocytes

D. An increase in basophils

13. D CML is marked by an elevated WBC count

demonstrating various stages of maturation,

hypermetabolism, and a minimal LAP staining.

An increase in basophils and eosinophils is a

common finding. Pseudo-Pelger-Huët cells and

thrombocytosis may be present. The marrow is

hypercellular with a high M:E ratio (e.g., 10:1).

14. In which of the following conditions does LAP

show the least activity?

A. Leukemoid reactions

B. Idiopathic myelofibrosis

C. PV

D. CML

14. D Chronic myelogenous leukemia shows the least LAP

activity, whereas the LAP score is slightly to markedly

increased in each of the other states

15. A striking feature of the peripheral blood of a

patient with CML is a:

A. Profusion of bizarre blast cells

B. Normal number of typical granulocytes

C. Presence of granulocytes at different stages of

development

D. Pancytopenia

15. C The WBC count in CML is often higher than 100 ×

109/L, and the peripheral smear shows a granulocyte

progression from myeloblast to segmented

neutrophil.

16. Which of the following is often associated with

CML but not with AML?

A. Infections

B. WBCs greater than 20.0 × 109/L

C. Hemorrhage

D. Splenomegaly

16. D Splenomegaly is seen in more than 90% of CML

patients, but it is not a characteristic finding in AML.

Infections, hemorrhage, and elevated WBC counts

may be seen in both CML and AML.

17. Multiple myeloma and Waldenström's

macroglobulinemia have all the following in

common except:

A. Monoclonal gammopathy

B. Hyperviscosity of the blood

C. Bence-Jones protein in the urine

D. Osteolytic lesions

17. D Osteolytic lesions indicating destruction of the

bone as evidenced by radiography are seen in

multiple myeloma but not in Waldenström's

macroglobulinemia. In addition, Waldenström's

gives rise to a lymphocytosis that does not occur

in multiple myeloma and differs in the morphology

of the malignant cells

18. What is the characteristic finding seen in the

peripheral smear of a patient with multiple

myeloma?

A. Microcytic hypochromic cells

B. Intracellular inclusion bodies

C. Rouleaux

D. Hypersegmented neutrophils

18. C Rouleaux is observed in multiple myeloma patients

as a result of increased viscosity and decreased

albumin/globulin ratio. Multiple myeloma is a

plasma cell dyscrasia that is characterized by an

overproduction of monoclonal immunoglobulin.

19. All of the following are associated with the

diagnosis of multiple myeloma except:

A. Marrow plasmacytosis

B. Lytic bone lesions

C. Serum and/or urine M component (monoclonal

protein)

D. Philadelphia chromosome

19. D The Ph1 chromosome is a diagnostic marker for CML.

Osteolytic lesions, monoclonal gammopathy, and

bone marrow infiltration by plasma cells constitute

the triad of diagnostic markers for multiple myeloma.

20. Multiple myeloma is most difficult to distinguish

from:

A. Chronic lymphocytic leukemia

B. Acute myelogenous leukemia

C. Benign monoclonal gammopathy

D. Benign adenoma

20. C Benign monoclonal gammopathies have peripheral

blood findings similar to those in myeloma. However,

a lower concentration of monoclonal protein is

usually seen. There are no osteolytic lesions, and the

plasma cells comprise less than 10% of nucleated

cells in the bone marrow. About 30% become

malignant, and therefore the term monoclonal

gammopathy of undetermined significance (MGUS) is

the designation used to describe this condition.

21. The pathology of multiple myeloma includes

which of the following?

A. Expanding plasma cell mass

B. Overproduction of monoclonal

immunoglobulins

C. Production of osteoclast activating factor (OAF)

and other cytokines

D. All of these options

21. D Mutated plasmablasts in the bone marrow undergo

clonal replication and expand the plasma cell mass.

Normal bone marrow is gradually replaced by the

malignant plasma cells leading to pancytopenia.

Most malignant plasma cells actively produce

immunoglobulins. In multiple myeloma, the normally

controlled and purposeful production of antibodies

is replaced by the inappropriate production of even

larger amounts of useless immunoglobulin

molecules. The normally equal production of light

chains and heavy chains may be imbalanced. The

result is the release of excess free light chains or free

heavy chains. The immunoglobulins produced by a

clone of myeloma cells are identical. Any abnormal

production of identical antibodies is referred to by

the general name of monoclonal gammopathy.

Osteoclasts are bone cells active in locally resorbing

bone and releasing calcium into the blood. Nearby

osteoblasts are equally active in utilizing calcium in

the blood to form new bone. Multiple myeloma

interrupts this balance by the secretion of at least

two substances. These are interleukin-6 (IL-6) and

osteoclast-activating factor (OAF). As its name

implies, OAF stimulates osteoclasts to increase bone

resorption and release of calcium, which leads to

lytic lesions of the bone.

22. Waldenström's macroglobulinemia is a

malignancy of the:

A. Lymphoplasmacytoid cells

B. Adrenal cortex

C. Myeloblastic cell lines

D. Erythroid cell precursors

22. A Waldenström's macroglobulinemia is a malignancy

of the lymphoplasmacytoid cells, which manufacture

IgM. Although the cells secrete immunoglobulin, they

are not fully differentiated into plasma cells and lack

the characteristic perinuclear halo, deep basophilia,

and eccentric nucleus characteristic of classic plasma

cells.

23. Cells that exhibit a positive stain with acid

phosphatase and are not inhibited with tartaric

acid are characteristically seen in:

A. Infectious mononucleosis

B. Infectious lymphocytosis

C. Hairy cell leukemia

D. T-cell acute lymphoblastic leukemia

23. C A variable number of malignant cells in hairy cell

leukemia (HCL) will stain positive with tartrateresistant

acid phosphatase (TRAP+). Although this

cytochemical reaction is fairly specific for HCL, TRAP

activity has occasionally been reported in B-cell and

rarely T-cell leukemia.

24. The JAK2(V617F) mutation may be positive in

all of the following chronic myeloproliferative

disorders except:

A. Essential thrombocythemia

B. Idiopathic myelofibrosis

C. PV

D. CML

24. D The JAK2(V617F) mutation is negative in patients

with CML. It may be positive in patients with

idiopathic myelofibrosis (35%-57%), polycythemia

vera (65%-97%), and essential thrombocythemia

(23%-57%).

25. All of the following are major criteria for the

2008 WHO diagnostic criteria for essential

thrombocythemia except:

A. Platelet count >450 × 109/L

B. Megakaryocyte proliferation with large and

mature morphology, and no or little granulocyte

or erythroid proliferation

C. Demonstration of JAK2(V617F) or other clonal

marker

D. Sustained platelet count >600 × 109/L

25. D The criterion for the 2001 WHO diagnosis of

essential thrombocythemia (ET) was a platelet count

≥600 x 109/L. This was changed in the 2008 WHO

criteria to ≥450 x 109 /L. Diagnosis of essential

thrombocythemia requires meeting all four major

2008 WHO diagnostic criteria, which also includes:

megakaryocyte proliferation with large and mature

morphology and no or little granulocyte or erythroid

proliferation; not meeting WHO criteria for CML,

PV, IMF, MDS, or other myeloid neoplasm; and

demonstration of JAK2(V617F) mutation or other

clonal marker, or no evidence of reactive

thrombocytosis.